The invention relates to lipid compositions and methods of using the lipid compositions for treatment of metabolic disorders, including diabetes and inflammatory bowel disease.
The orphan nuclear receptor LRH-1/NR5A2 is expressed in the liver, intestine, exocrine pancreas, and ovary. It binds DNA as a monomer and is best known as a regulator of hepatic expression of the key bile acid biosynthetic enzyme Cyp7A1 but is also reported to regulate expression of a number of other genes associated with bile acid and cholesterol homeostasis, as well as other metabolic targets. It is expressed in embryonic stem cells and initial stages of embryonic development. The very early lethality of LRH-1 null mice both highlights its essential developmental role and precludes straightforward knockout studies that have been so useful for delineating the functions of other orphan and former orphan receptors.
Analysis of LRH-1 function has also been hindered by the absence of appropriate agonist or antagonist ligands. A series of crystal structures of LRH-1 and its closest relative SF-1 (NR5A1) has recently identified phospholipids as potential ligands, but their function as modulators of receptor signaling has remained uncertain.
Thus, additional agonists for LRH-1 would be highly desirable.